U.S. patent application number 16/841735 was filed with the patent office on 2020-08-13 for oral care compositions and methods of use.
This patent application is currently assigned to Colgate-Palmolive Company. The applicant listed for this patent is Colgate-Palmolive Company. Invention is credited to Rehana BEGUM-GAFUR, Michael PRENCIPE, Aarti REGE, Paul THOMSON.
Application Number | 20200253844 16/841735 |
Document ID | 20200253844 / US20200253844 |
Family ID | 1000004782517 |
Filed Date | 2020-08-13 |
Patent Application | download [pdf] |
United States Patent
Application |
20200253844 |
Kind Code |
A1 |
REGE; Aarti ; et
al. |
August 13, 2020 |
Oral Care Compositions and Methods of Use
Abstract
This invention relates to oral care compositions comprising zinc
phosphate, a first source of stannous (e.g., stannous fluoride);
and a second source of stannous, wherein the second source of
stannous comprises stannous pyrophosphate, as well as to methods of
using and of making these compositions.
Inventors: |
REGE; Aarti; (East Windsor,
NJ) ; PRENCIPE; Michael; (West Windsor, NJ) ;
THOMSON; Paul; (Piscataway, NJ) ; BEGUM-GAFUR;
Rehana; (Clifton, NJ) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Colgate-Palmolive Company |
New York |
NY |
US |
|
|
Assignee: |
Colgate-Palmolive Company
New York
NY
|
Family ID: |
1000004782517 |
Appl. No.: |
16/841735 |
Filed: |
April 7, 2020 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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15848009 |
Dec 20, 2017 |
10646420 |
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16841735 |
|
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62437091 |
Dec 21, 2016 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61K 8/27 20130101; A61K
8/24 20130101; A61Q 11/00 20130101; A61K 8/20 20130101; A61K 8/21
20130101 |
International
Class: |
A61K 8/24 20060101
A61K008/24; A61Q 11/00 20060101 A61Q011/00; A61K 8/21 20060101
A61K008/21; A61K 8/27 20060101 A61K008/27; A61K 8/20 20060101
A61K008/20 |
Claims
1. An oral care composition comprising: a zinc source comprising
zinc phosphate; a first source of stannous, wherein the stannous
comprises stannous fluoride; and a second source of stannous,
wherein the second source of stannous comprises stannous
pyrophosphate.
2. The oral care composition of claim 1, wherein the zinc phosphate
is a preformed salt of zinc phosphate.
3. The oral care composition of claim 1, wherein the zinc phosphate
is present in an amount sufficient so that the stannous fluoride
dissociates to provide a therapeutically effective amount of
stannous ions in aqueous solution.
4. The oral care composition of claim 1, wherein the amount of zinc
phosphate is from 0.05 to 10% by weight, relative to the weight of
the oral care composition.
5. The composition of claim 1, wherein the first stannous ion
source further comprises other stannous halides such as stannous
chloride dihydrate, stannous pyrophosphate, organic stannous
carboxylate salts such as stannous formate, acetate, gluconate,
lactate, tartrate, oxalate, malonate and citrate, stannous ethylene
glyoxide, or a mixture thereof.
6. The composition of claim 1, wherein the first stannous ion
source is stannous fluoride.
7. The composition of claim 1, wherein the composition comprises an
effective amount of one or more alkali phosphate salts, e.g.,
sodium, potassium or calcium salts, e.g., selected from alkali
dibasic phosphate and alkali pyrophosphate salts, e.g., alkali
phosphate salts selected from sodium phosphate dibasic, potassium
phosphate dibasic, dicalcium phosphate dihydrate, calcium
pyrophosphate, tetrasodium pyrophosphate, tetrapotassium
pyrophosphate, sodium tripolyphosphate, disodium hydrogen
orthophosphate, monosodium phosphate, pentapotassium triphosphate
and mixtures of any of two or more of these by weight of the
composition.
8. The composition of claim 1, wherein the alkali phosphate salt is
tetrapotassium pyrophosphate.
9. The composition of claim 1, wherein the alkali phosphate salt is
sodium tripolyphosphate.
10. The composition of claim 1, wherein the composition
comprises:
11. The composition of claim 1, wherein the composition comprises:
a. Zinc phosphate about 1.0 wt % b. Stannous pyrophosphate about
0.2 wt % c. Tetrasodium pyrophosphate about 2.0 wt %
12. The composition of claim 1, wherein the composition comprises:
a. Zinc phosphate about 1.0 wt % b. Stannous pyrophosphate about
0.3 wt % c. Tetrasodium pyrophosphate about 2.0 wt %
13. The composition of claim 1, wherein the composition comprises:
a. Zinc phosphate about 1.7 wt % b. Stannous pyrophosphate about
1.0 wt % c. Tetrasodium pyrophosphate about 2.0 wt %
14. The composition of claim 1, further comprising a citrate buffer
system, wherein the buffer system comprises tri-sodium citrate and
citric acid.
15. A method to improve oral health comprising applying an
effective amount of the oral composition of claim 1, wherein the
oral care composition is applied to the oral cavity of a subject in
need thereof.
Description
CROSS-REFERENCE TO RELATED PATENT APPLICATIONS
[0001] This application claims priority from U.S. Prov. Appl. No.
62/437,091, filed on Dec. 21, 2016, the contents of which are
incorporated herein by reference in their entirety.
FIELD
[0002] This invention relates to oral care compositions comprising
zinc phosphate a first stannous ion source, and a second stannous
ion source, wherein the second stannous ion comprises stannous
pyrophosphate, as well as to methods of using and making these
compositions.
BACKGROUND
[0003] Oral care compositions present particular challenges in
preventing microbial contamination.
[0004] Zinc is a known antimicrobial agent used in toothpaste
compositions. Zinc is a known essential mineral for human health,
and has been reported to help strengthen dental enamel and to
promote cell repair. Unfortunately, conventional toothpaste
formulations often require high concentrations of zinc, e.g., 2% by
weight or more, to achieve efficacy. At this concentration, the
zinc imparts a notably astringent taste to the composition. There
is thus a need for improved antibacterial toothpaste formulations
that do not suffer from the drawbacks of conventional
compositions.
[0005] Stannous ions, in particular stannous salts such as stannous
fluoride, are also known anti-microbial agents and are used in
various dentifrices as agents for preventing plaque. However, there
are certain disadvantages to using stannous salts, such as
instability, tendency to stain teeth, astringency, and unpleasant
taste for users.
[0006] Zinc phosphate (Zn.sub.3(PO.sub.4).sub.2) is insoluble in
water, although soluble in acidic or basic solutions, e.g.,
solutions of mineral acids, acetic acid, ammonia, or alkali
hydroxides. See, e.g., Merck Index, 13.sup.th Ed. (2001) p. 1812,
monograph number 10205. Partly because it is viewed in the art as a
generally inert material, zinc phosphate is commonly used in dental
cements, for example in cementation of inlays, crowns, bridges, and
orthodontic appliances, which are intended to endure in the mouth
for many years. Zinc phosphate dental cements are generally
prepared by mixing zinc oxide and magnesium oxide powders with a
liquid consisting principally of phosphoric acid, water, and
buffers, so the cement comprising zinc phosphate is formed in situ
by reaction with phosphoric acid.
[0007] Oral care compositions which contain stannous ion sources
exhibit excellent clinical benefits, particularly in the reduction
of gingivitis and in the treatment or prevention of erosive tooth
demineralization. Stannous fluoride is well known for use in
clinical dentistry with a history of therapeutic benefits over
forty years. However, until recently, its popularity has been
limited by its instability in aqueous solutions. The instability of
stannous fluoride in water is primarily due to the reactivity of
the stannous ion (Sn.sup.2+). Stannous salts readily hydrolyse
above a pH of 4, resulting in precipitation from solution, with a
consequent loss of the therapeutic properties.
[0008] One way to overcome the stability problems with stannous
ions is to limit the amount of water in the composition to very low
levels, or to use a dual phase system. Both of these solutions to
the stannous ion problem have drawbacks. Low water oral care
compositions can be difficult to formulate with desired rheological
properties, and dual-phase compositions are considerably more
expensive to manufacture and package.
[0009] Accordingly, in view of the drawbacks and disadvantages to
using various antimicrobials, such as zinc and stannous, there is a
need for oral care compositions with anti-bacterial efficacy, but
which are also palatable and desirable for a user.
BRIEF SUMMARY
[0010] The inclusion of a zinc source comprising zinc phosphate,
selected at certain concentrations and amounts, increases or
improves the delivery of stannous in the oral cavity of a user. The
delivery or availability of Sn is improved in the current
invention, where the improvement is relative to comparable products
currently on the market.
[0011] In one aspect the invention is an oral care composition
(Composition 1.0) comprising: [0012] A zinc source comprising zinc
phosphate; [0013] a first source of stannous (e.g., stannous
fluoride); and [0014] a second source of stannous, wherein the
second source of stannous comprises stannous pyrophosphate.
[0015] For example, the invention contemplates any of the following
compositions (unless otherwise indicated, values are given as
percentage of the overall weight of the composition) [0016] 1.1
Composition 1, wherein the zinc phosphate is a preformed salt of
zinc phosphate (e.g., zinc phosphate hydrate). [0017] 1.2 Any
preceding composition, wherein the amount of zinc phosphate is from
0.05 to 10% by weight, relative to the weight of the oral care
composition, for example, from 0.1 to 8% by weight, or from 0.5 to
5% by weight, or from 0.5 to 4% by weight, or from 1 to 4%, or from
1 to 3% by weight, or from 2 to 3% by weight, or about 1% or about
2%, or about 2.25% or about 2.5%, by weight. [0018] 1.3 Any of the
preceding compositions, wherein the amount of stannous
pyrophosphate is from 0.1%-3% by wt. of the composition. (e.g.,
about 1% by wt. of the composition). [0019] 1.4 Any of the
preceeding compositions wherein the amount of stannous
pyrophosphate is about 0.2% by wt. [0020] 1.5 Any of the
compositions 1.1-1.4 wherein the amount of stannous pyrophosphate
is about 0.3% by wt. [0021] 1.6 Any of the compositions 1.1-1.4
wherein the amount of stannous pyrophosphate is about 0.5% by wt.
[0022] 1.7 Any of the compositions 1.1-1.4 wherein the amount of
stannous pyrophosphate is about 0.75% by wt. [0023] 1.8 Any of the
compositions 1.1-1.4 wherein the amount of stannous pyrophosphate
is about 1.0% by wt. [0024] 1.9 Any of the preceding composition,
wherein the first stannous ion source is stannous fluoride, other
stannous halides such as stannous chloride dihydrate, stannous
pyrophosphate, organic stannous carboxylate salts such as stannous
formate, acetate, gluconate, lactate, tartrate, oxalate, malonate
and citrate, stannous ethylene glyoxide, or a mixture thereof.
[0025] 1.10 Composition of 1.14, wherein the first stannous ion
source is stannous fluoride (e.g., about 0.45 wt %; e.g., about
0.454 wt %.) [0026] 1.11 Any of the preceding compositions further
comprising a fluoride source selected from: stannous fluoride,
sodium fluoride, potassium fluoride, sodium monofluorophosphate,
sodium fluorosilicate, ammonium fluorosilicate, amine fluoride
(e.g.,
N'-octadecyltrimethylendiamine-N,N,N'-tris(2-ethanol)-dihydrofluoride),
ammonium fluoride, titanium fluoride, hexafluorosulfate, and
combinations thereof [0027] 1.12 Any of the preceding compositions
wherein the pH is between 7.5 and 10.5. [0028] 1.13 Any of the
preceding compositions further comprising an effective amount of
one or more alkali phosphate salts, e.g., sodium, potassium or
calcium salts, e.g., selected from alkali dibasic phosphate and
alkali pyrophosphate salts, e.g., alkali phosphate salts selected
from sodium phosphate dibasic, potassium phosphate dibasic,
dicalcium phosphate dihydrate, calcium pyrophosphate, tetrasodium
pyrophosphate, tetrapotassium pyrophosphate, sodium
tripolyphosphate, disodium hydrogen orthophosphate, monosodium
phosphate, pentapotassium triphosphate and mixtures of any of two
or more of these, e.g., in an amount of 1-20%, e.g., 2-8%, e.g.,
ca. 5%>, by weight of the composition. [0029] 1.14 The alkali
phosphate salt of 1.13, wherein the salt comprises tetrapotassium
pyrophosphate [0030] 1.15 The composition of 1.14, wherein the
tetrasodium pyrophosphate is from 0.1-3.0 wt % (e.g., about 2.0 wt
%). [0031] 1.16 The composition of 1.13, wherein the salt comprises
sodium tripolyphosphate. [0032] 1.17 The composition of 1.16,
wherein sodium tripolyphosphate is from 0.1-3.0 wt % (e.g., about
2.0 wt %). [0033] 1.18 Any of the preceding compositions further
comprising an abrasive or particulate (e.g., silica). [0034] 1.19
Any of the preceding compositions wherein the silica is synthetic
amorphous silica. (e.g., 1%-28% by wt.) (e.g., 8%-25% by wt.)
[0035] 1.20 Any of the preceding composition wherein the silica
abrasives are silica gels or precipitated amorphous silicas, e.g.
silicas having an average particle size ranging from 2.5 microns to
12 microns. [0036] 1.21 Any of the preceding compositions further
comprising a small particle silica having a median particle size
(d50) of 1-5 microns (e.g., 3-4 microns) (e.g., about 5 wt. %
Sorbosil AC43 from PQ Corporation, Warrington, United Kingdom).
[0037] 1.22 Any of the preceding compositions wherein 20-30 wt % of
the total silica in the composition is small particle silica (e.g.,
having a median particle size (d50) of 3-4 microns) and wherein the
small particle silica is about 5 wt. % of the oral care
composition. [0038] 1.23 Any of the preceding compositions
comprising silica wherein the silica is used as a thickening agent,
e.g., particle silica. [0039] 1.24 Any of the preceding
compositions further comprising glycerin, wherein the glycerin is
in a total amount of 2.0-5.0% (e.g., about 4%) [0040] 1.25 The
composition of 1.24, wherein the glycerin is in an amount of about
4% by wt. of the composition. [0041] 1.26 Any of the preceding
compositions, wherein the composition comprises an aqueous buffer
system, for example, wherein the buffer system comprises an organic
acid and an alkali metal salt thereof, e.g., wherein the organic
acid is citric acid and the salt is a mono-, di- and/or tri-alkali
metal citrate salt, e.g., mono-, di- and/or tri-lithium, sodium,
potassium, or cesium citrate salt, and citric acid.) [0042] 1.27
Composition of 1.26, wherein the buffer system comprises trisodium
citrate and citric acid (e.g., 1 to 10% by weight of the
composition) (e.g., 1.2% by wt. of the composition). For example,
the molar ratio of mono-, di- and/or tri-sodium citrate and citric
acid is 1.5 to 5, (e.g., 2 to 4). [0043] 1.28 Composition of 1.26
or 1.27, wherein the buffer is a citrate buffer comprising sodium
citrate (e.g., about 1.0% wt.) and citric acid (e.g., about 0.2%
wt.) [0044] 1.29 Any of the preceding compositions comprising
polymer films. [0045] 1.30 Any of the preceding compositions
comprising flavoring, fragrance and/or coloring. [0046] 1.31 Any of
the preceding compositions, wherein the composition comprises a
thickening agents selected from the group consisting of
carboxyvinyl polymers, carrageenan, hydroxyethyl cellulose and
water soluble salts of cellulose ethers (e.g., sodium carboxymethyl
cellulose and sodium carboxymethyl hydroxyethyl cellulose). [0047]
1.32 Any of the preceding compositions, wherein the compositions
comprises sodium carboxymethyl cellulose (e.g., from 0.5 wt. %-1.5
wt. %) [0048] 1.33 Any of the preceding compositions comprising
from 5%-40%, e.g., 10%-35%, e.g., about 10%, 15%, 25%, 30%, and 35%
water. [0049] 1.34 Any of the preceding compositions comprising an
additional antibacterial agent selected from halogenated diphenyl
ether (e.g. triclosan), herbal extracts and essential oils (e.g.,
rosemary extract, tea extract, magnolia extract, thymol, menthol,
eucalyptol, geraniol, carvacrol, citral, hinokitol, catechol,
methyl salicylate, epigallocatechin gallate, epigallocatechin,
gallic acid, miswak extract, sea-buckthorn extract), bisguanide
antiseptics (e.g., chlorhexidine, alexidine or octenidine),
quaternary ammonium compounds (e.g., cetylpyridinium chloride
(CPC), benzalkonium chloride, tetradecylpyridinium chloride (TPC),
N-tetradecyl-4-ethylpyridinium chloride (TDEPC)), phenolic
antiseptics, hexetidine, octenidine, sanguinarine, povidone iodine,
delmopinol, salifluor, metal ions (e.g., zinc salts, for example,
Zinc Chloride, Zinc Lactate, Zinc Sulfate, stannous salts, copper
salts, iron salts), sanguinarine, propolis and oxygenating agents
(e.g., hydrogen peroxide, buffered sodium peroxyborate or
peroxycarbonate), phthalic acid and its salts, monoperthalic acid
and its salts and esters, ascorbyl stearate, oleoyl sarcosine,
alkyl sulfate, dioctyl sulfosuccinate, salicylanilide, domiphen
bromide, delmopinol, octapinol and other piperidino derivatives,
nicin preparations, chlorite salts; and mixtures of any of the
foregoing. [0050] 1.35 Any of the preceding compositions comprising
an antioxidant, e.g., selected from the group consisting of
Co-enzyme Q10, PQQ, Vitamin C, Vitamin E, Vitamin A, BHT,
anethole-dithiothione, and mixtures thereof. [0051] 1.36 Any of the
preceding compositions comprising a whitening agent. [0052] 1.37
Any of the preceding compositions comprising a whitening agent
selected from a whitening active selected from the group consisting
of peroxides, metal chlorites, perborates, percarbonates,
peroxyacids, hypochlorites, and combinations thereof. [0053] 1.38
The composition of 1.36, wherein the whitening agent is titanium
dioxide. [0054] 1.39 Any of the preceding compositions further
comprising hydrogen peroxide or a hydrogen peroxide source, e.g.,
urea peroxide or a peroxide salt or complex (e.g., such as
peroxyphosphate, peroxycarbonate, perborate, peroxysilicate, or
persulphate salts; for example calcium peroxyphosphate, sodium
perborate, sodium carbonate peroxide, sodium peroxyphosphate, and
potassium persulfate), or hydrogen peroxide polymer complexes such
as hydrogen peroxide-polyvinyl pyrrolidone polymer complexes.
[0055] 1.40 Any of the preceding compositions further comprising an
anionic surfactant, e.g., (e.g., sodium lauryl sulfate). [0056]
1.41 Any of the preceding compositions further comprising
microcrystalline cellulose and/or sodium carboxymethylcellulose,
e.g., in an amount of from 0.1-5%, e.g., 0.5-2%, e.g. 1%. [0057]
1.42 Any of the preceding compositions further comprising
polyethylene glycol in an amount of from 1-6% (e.g., 2% wt.).
[0058] 1.43 Any of the preceding compositions further comprising an
agent that interferes with or prevents bacterial attachment, e.g.,
ELA or chitosan. [0059] 1.44 Any of the preceding compositions
comprising: [0060] Zinc phosphate about 1.0 wt % [0061] Stannous
pyrophosphate about 0.2 wt % [0062] Tetrasodium pyrophosphate about
2.0 wt % [0063] 1.45 Any of the preceding compositions comprising:
[0064] Zinc phosphate about 1.0 wt % [0065] Stannous pyrophosphate
about 0.3 wt % [0066] Tetrasodium pyrophosphate about 2.0 wt %
[0067] 1.46 Any of 1.0-1.43, wherein the composition comprises
[0068] Zinc phosphate about 1.7 wt % [0069] Stannous pyrophosphate
about 1.0 wt % [0070] Tetrasodium pyrophosphate about 2.0 wt %
[0071] 1.47 Any of Composition 1.44-1.46 further comprising a
citrate buffer system, wherein the buffer system comprises
tri-sodium citrate and citric acid (e.g., the buffer system being
about 1.2 wt % of the composition). [0072] 1.48 Any of the
preceding compositions effective upon application to the oral
cavity, e.g., by rinsing, optionally in conjunction with brushing,
to (i) reduce or inhibit formation of dental caries, (ii) reduce,
repair or inhibit pre-carious lesions of the enamel, e.g., as
detected by quantitative light-induced fluorescence (QLF) or
electrical caries measurement (ECM), (iii) reduce or inhibit
demineralization and promote remineralization of the teeth, (iv)
reduce hypersensitivity of the teeth, (v) reduce or inhibit
gingivitis, (vi) promote healing of sores or cuts in the mouth,
(vii) reduce levels of acid producing bacteria, (viii) to increase
relative levels of arginolytic bacteria, (ix) inhibit microbial
biofilm formation in the oral cavity, (x) raise and/or maintain
plaque pH at levels of at least pH 5.5 following sugar challenge,
(xi) reduce plaque accumulation, (xii) treat, relieve or reduce dry
mouth, (xiii) clean the teeth and oral cavity (xiv) reduce erosion,
(xv) prevents stains and/or whiten teeth, (xvi) immunize the teeth
against cariogenic bacteria; and/or (xvii) promote systemic health,
including cardiovascular health, e.g., by reducing potential for
systemic infection via the oral tissues. [0073] 1.49 Any of the
preceding oral compositions, wherein the oral composition may be
any of the following oral compositions selected from the group
consisting of: a toothpaste or a dentifrice, a mouthwash or a mouth
rinse, a topical oral gel, and a denture cleanser. [0074] 1.50 A
composition obtained or obtainable by combining the ingredients as
set forth in any of the preceding compositions. [0075] 1.51 Any
preceding compositions, wherein zinc phosphate is the only source
of zinc. [0076] 1.52 Any of the preceding compositions, wherein
stannous fluoride and stannous pyrophosphate are the only sources
of stannous. [0077] 1.53 Any of the preceding compositions, wherein
the humectant is selected from the group consisting of: edible
polyhydric alcohols (e.g., glycerin, sorbitol, xylitol, propylene
glycol), polyols and mixtures thereof. [0078] 1.54 Any of the
preceding compositions, wherein the humectant is sorbitol (e.g.,
about 40 wt. %, about 41%, or about 42 wt. %) [0079] 1.55 A
composition obtained or obtainable by combining the ingredients as
set forth in any of the preceding compositions. [0080] 1.56 A
composition for use as set for in any of the preceding
compositions.
[0081] In another embodiment, the invention encompasses a method to
improve oral health comprising applying an effective amount of the
oral composition of any of the embodiments set forth above to the
oral cavity of a subject in need thereof, e.g., a method to [0082]
i. reduce or inhibit formation of dental caries, [0083] ii. reduce,
repair or inhibit early enamel lesions, e.g., as detected by
quantitative light-induced fluorescence (QLF) or electrical caries
measurement(ECM), [0084] iii. reduce or inhibit demineralization
and promote remineralization of the teeth, [0085] iv. reduce
hypersensitivity of the teeth, [0086] v. reduce or inhibit
gingivitis, [0087] vi. promote healing of sores or cuts in the
mouth, [0088] vii. reduce levels of acid producing bacteria, [0089]
viii. to increase relative levels of arginolytic bacteria, [0090]
ix. inhibit microbial bio film formation in the oral cavity, [0091]
x. raise and/or maintain plaque pH at levels of at least pH 5.5
following sugar challenge, [0092] xi. reduce plaque accumulation,
[0093] xii. treat dry mouth, [0094] xiii. enhance systemic health,
including cardiovascular health, e.g., by reducing potential for
systemic infection via the oral tissues, [0095] xiv. Whiten teeth,
[0096] xv. reduce erosion of the teeth, [0097] xvi. immunize (or
protect) the teeth against cariogenic bacteria and their effects,
and/or [0098] xvii. clean the teeth and oral cavity. The invention
further comprises the use of sodium bicarbonate, sodium methyl
cocoyl taurate (tauranol), MIT, and benzyl alcohol and combinations
thereof in the manufacture of a Composition of the Invention, e.g.,
for use in any of the indications set forth in the above method of
Composition 1.0, et seq.
DETAILED DESCRIPTION
[0099] As used herein, the term "oral composition" means the total
composition that is delivered to the oral surfaces. The composition
is further defined as a product which, during the normal course of
usage, is not, the purposes of systemic administration of
particular therapeutic agents, intentionally swallowed but is
rather retained in the oral cavity for a time sufficient to contact
substantially all of the dental surfaces and/or oral tissues for
the purposes of oral activity. Examples of such compositions
include, but are not limited to, toothpaste or a dentifrice, a
mouthwash or a mouth rinse, a topical oral gel, a denture cleanser,
and the like.
[0100] As used herein, the term "dentifrice" means paste, gel, or
liquid formulations unless otherwise specified. The dentifrice
composition can be in any desired form such as deep striped,
surface striped, multi-layered, having the gel surrounding the
paste, or any combination thereof. Alternatively the oral
composition may be dual phase dispensed from a separated
compartment dispenser.
Stannous Ion Source
[0101] In some embodiments, the first stannous source comprises a
stannous source selected from stannous fluoride, other stannous
halides such as stannous chloride dihydrate, stannous
pyrophosphate, organic stannous carboxylate salts such as stannous
formate, acetate, gluconate, lactate, tartrate, oxalate, malonate
and citrate, stannous ethylene glyoxide, or mixtures thereof. In
some embodiments, the first stannous source comprises stannous
fluoride.
Fluoride Ion Source
[0102] The oral care compositions may further include one or more
fluoride ion sources, e.g., soluble fluoride salts. A wide variety
of fluoride ion-yielding materials can be employed as sources of
soluble fluoride in the present compositions. Examples of suitable
fluoride ion-yielding materials are found in U.S. Pat. No.
3,535,421, to Briner et al.; U.S. Pat. No. 4,885,155, to Parran,
Jr. et al. and U.S. Pat. No. 3,678,154, to Widder et al., each of
which are incorporated herein by reference. Representative fluoride
ion sources used with the present invention (e.g., Composition 1.0
et seq.) include, but are not limited to, stannous fluoride, sodium
fluoride, potassium fluoride, sodium monofluorophosphate, sodium
fluorosilicate, ammonium fluorosilicate, amine fluoride, ammonium
fluoride, and combinations thereof. In certain embodiments the
fluoride ion source includes stannous fluoride, sodium fluoride,
sodium monofluorophosphate as well as mixtures thereof. Where the
formulation comprises calcium salts, the fluoride salts are
preferably salts wherein the fluoride is covalently bound to
another atom, e.g., as in sodium monofluorophosphate, rather than
merely ionically bound, e.g., as in sodium fluoride.
Surfactants
[0103] The invention may in some embodiments contain anionic
surfactants, e.g., the Compositions of Composition 1.0, et seq.,
for example, water-soluble salts of higher fatty acid monoglyceride
monosulfates, such as the sodium salt of the monosulfated
monoglyceride of hydrogenated coconut oil fatty acids such as
sodium N-methyl N-cocoyl taurate, sodium cocomo-glyceride sulfate;
higher alkyl sulfates, such as sodium lauryl sulfate; higher
alkyl-ether sulfates, e.g., of formula
CH.sub.3(CH.sub.2).sub.mCH.sub.2(OCH.sub.2CH.sub.2).sub.nOS0.sub.3X,
wherein m is 6-16, e.g., 10, n is 1-6, e.g., 2, 3 or 4, and X is Na
or, for example sodium laureth-2 sulfate
(CH.sub.3(CH2).sub.10CH.sub.2(OCH.sub.2CH.sub.2).sub.2OS0.sub.3Na);
higher alkyl aryl sulfonates such as sodium dodecyl benzene
sulfonate (sodium lauryl benzene sulfonate); higher alkyl
sulfoacetates, such as sodium lauryl sulfoacetate (dodecyl sodium
sulfoacetate), higher fatty acid esters of 1,2 dihydroxy propane
sulfonate, sulfocolaurate (N-2-ethyl laurate potassium
sulfoacetamide) and sodium lauryl sarcosinate. By "higher alkyl" is
meant, e.g., C.sub.6-30 alkyl. In particular embodiments, the
anionic surfactant (where present) is selected from sodium lauryl
sulfate and sodium ether lauryl sulfate. When present, the anionic
surfactant is present in an amount which is effective, e.g.,
>0.001% by weight of the formulation, but not at a concentration
which would be irritating to the oral tissue, e.g., 1%, and optimal
concentrations depend on the particular formulation and the
particular surfactant. In one embodiment, the anionic surfactant is
present at from 0.03% to 5% by weight, e.g., 1.5%.
[0104] In another embodiment, cationic surfactants useful in the
present invention can be broadly defined as derivatives of
aliphatic quaternary ammonium compounds having one long alkyl chain
containing 8 to 18 carbon atoms such as lauryl trimethylammonium
chloride, cetyl pyridinium chloride, cetyl trimethylammonium
bromide, di-isobutylphenoxyethyldimethylbenzylammonium chloride,
coconut alkyltrimethylammonium nitrite, cetyl pyridinium fluoride,
and mixtures thereof. Illustrative cationic surfactants are the
quaternary ammonium fluorides described in U.S. Pat. No. 3,535,421,
to Briner et al., herein incorporated by reference. Certain
cationic surfactants can also act as germicides in the
compositions.
[0105] Illustrative nonionic surfactants of Composition 1.0, et
seq., that can be used in the compositions of the invention can be
broadly defined as compounds produced by the condensation of
alkylene oxide groups (hydrophilic in nature) with an organic
hydrophobic compound which may be aliphatic or alkylaromatic in
nature. Examples of suitable nonionic surfactants include, but are
not limited to, the Pluronics, polyethylene oxide condensates of
alkyl phenols, products derived from the condensation of ethylene
oxide with the reaction product of propylene oxide and ethylene
diamine, ethylene oxide condensates of aliphatic alcohols, long
chain tertiary amine oxides, long chain tertiary phosphine oxides,
long chain dialkyl sulfoxides and mixtures of such materials.
[0106] Illustrative amphoteric surfactants of Composition 1.0, et
seq., that can be used in the compositions of the invention include
betaines (such as cocamidopropylbetaine), derivatives of aliphatic
secondary and tertiary amines in which the aliphatic radical can be
a straight or branched chain and wherein one of the aliphatic
substituents contains about 8-18 carbon atoms and one contains an
anionic water-solubilizing group (such as carboxylate, sulfonate,
sulfate, phosphate or phosphonate), and mixtures of such
materials.
[0107] The surfactant or mixtures of compatible surfactants can be
present in the compositions of the present invention in 0.1% to 5%,
in another embodiment 0.3% to 3% and in another embodiment 0.5% to
2% by weight of the total composition.
Flavoring Agents
[0108] The oral care compositions of the invention may also include
a flavoring agent. Flavoring agents which are used in the practice
of the present invention include, but are not limited to, essential
oils and various flavoring aldehydes, esters, alcohols, and similar
materials, as well as sweeteners such as sodium saccharin. Examples
of the essential oils include oils of spearmint, peppermint,
wintergreen, sassafras, clove, sage, eucalyptus, marjoram,
cinnamon, lemon, lime, grapefruit, and orange. Also useful are such
chemicals as menthol, carvone, and anethole. Certain embodiments
employ the oils of peppermint and spearmint.
[0109] The flavoring agent is incorporated in the oral composition
at a concentration of 0.01 to 1% by weight.
Chelating and Anti-Calculus Agents
[0110] The oral care compositions of the invention also may include
one or more chelating agents able to complex calcium found in the
cell walls of the bacteria. Binding of this calcium weakens the
bacterial cell wall and augments bacterial lysis.
[0111] Another group of agents suitable for use as chelating or
anti-calculus agents in the present invention are the soluble
pyrophosphates. The pyrophosphate salts used in the present
compositions can be any of the alkali metal pyrophosphate salts. In
certain embodiments, salts include tetra alkali metal
pyrophosphate, dialkali metal diacid pyrophosphate, trialkali metal
monoacid pyrophosphate and mixtures thereof, wherein the alkali
metals are sodium or potassium. The salts are useful in both their
hydrated and unhydrated forms. An effective amount of pyrophosphate
salt useful in the present composition is generally enough to
provide at least 0.1 wt. % pyrophosphate ions, e.g., 0.1 to 3 wt 5,
e.g., 0.1 to 2 wt %, e.g., 0.1 to 1 wt %, e.g., 0.2 to 0.5 wt %.
The pyrophosphates also contribute to preservation of the
compositions by lowering water activity.
[0112] In various embodiments of the present disclosure (e.g.,
Composition 1.0 et seq), the compositions further comprise one or
more anticalculus (tartar control) agents. Suitable anticalculus
agents include without limitation mono-phosphates (e.g. monobasic,
dibasic or tribasic phosphate) and P1-6 polyphosphates (e.g.,
pyrophosphates, tripolyphosphate, tetraphosphates and
hexametaphosphate salts, zinc salts (e.g., zinc citrate, zinc
chloride, zinc citrate trihydrate), Gantrez.RTM. (a copolymer of
methylvinyl ether (PVM) and maleic acid (MA)),
polyaminopropanesulfonic acid (AMPS), polypeptides, polyolefin
sulfonates, polyolefin phosphates, and diphosphonates. In certain
embodiments, the other anticalculus agents are alkali and/or
alkaline earth metal phosphate salts, for example, sodium,
potassium or calcium salts. In certain embodiments, the composition
includes mono-phosphates (e.g. monobasic, dibasic or tribasic
phosphate), P1-6 polyphosphates, Gantrez, or a combination thereof.
Still in certain embodiments, the composition includes sodium
tripolyphosphate, tetrasodium pyrophosphate, Gantrez, or a
combination thereof
Polymers
[0113] The oral care compositions of the invention also optionally
include one or more polymers, such as polyethylene glycols,
polyvinyl methyl ether maleic acid copolymers, polysaccharides
(e.g., cellulose derivatives, for example carboxymethyl cellulose,
or polysaccharide gums, for example xanthan gum or carrageenan
gum). Acidic polymers, for example polyacrylate gels, may be
provided in the form of their free acids or partially or fully
neutralized water soluble alkali metal (e.g., potassium and sodium)
or ammonium salts. Certain embodiments include 1:4 to 4:1
copolymers of maleic anhydride or acid with another polymerizable
ethylenically unsaturated monomer, for example, methyl vinyl ether
(methoxyethylene) having a molecular weight (M.W.) of about 30,000
to about 1,000,000. These copolymers are available for example as
Gantrez AN 139(M.W. 500,000), AN 1 19 (M.W. 250,000) and S-97
Pharmaceutical Grade (M.W. 70,000), of GAF Chemicals
Corporation.
[0114] Other operative polymers include those such as the 1:1
copolymers of maleic anhydride with ethyl acrylate, hydroxyethyl
methacrylate, N-vinyl-2-pyrollidone, or ethylene, the latter being
available for example as Monsanto EMA No. 1 103, M.W. 10,000 and
EMA Grade 61, and 1:1 copolymers of acrylic acid with methyl or
hydroxyethyl methacrylate, methyl or ethyl acrylate, isobutyl vinyl
ether or N-vinyl-2-pyrrolidone.
[0115] Suitable generally, are polymerized olefinically or
ethylenically unsaturated carboxylic acids containing an activated
carbon-to-carbon olefinic double bond and at least one carboxyl
group, that is, an acid containing an olefinic double bond which
readily functions in polymerization because of its presence in the
monomer molecule either in the alpha-beta position with respect to
a carboxyl group or as part of a terminal methylene grouping.
Illustrative of such acids are acrylic, methacrylic, ethacrylic,
alpha-chloroacrylic, crotonic, beta-acryloxy propionic, sorbic,
alpha-chlorsorbic, cinnamic, beta-styrylacrylic, muconic, itaconic,
citraconic, mesaconic, glutaconic, aconitic, alpha-phenylacrylic,
2-benzyl acrylic, 2-cyclohexylacrylic, angelic, umbellic, fumaric,
maleic acids and anhydrides. Other different olefinic monomers
copolymerizable with such carboxylic monomers include vinylacetate,
vinyl chloride, dimethyl maleate and the like. Copolymers contain
sufficient carboxylic salt groups for water-solubility.
[0116] A further class of polymeric agents includes a composition
containing homopolymers of substituted acrylamides and/or
homopolymers of unsaturated sulfonic acids and salts thereof, in
particular where polymers are based on unsaturated sulfonic acids
selected from acrylamidoalykane sulfonic acids such as 2-acrylamide
2 methylpropane sulfonic acid having a molecular weight of about
1,000 to about 2,000,000, described in U.S. Pat. No. 4,842,847,
Jun. 27, 1989 to Zahid, incorporated herein by reference.
[0117] In preparing oral care compositions, it is sometimes
necessary to add some thickening material to provide a desirable
consistency or to stabilize or enhance the performance of the
formulation. In certain embodiments, the thickening agents are
carboxyvinyl polymers, carrageenan, xanthan, hydroxyethyl cellulose
and water soluble salts of cellulose ethers such as sodium
carboxymethyl cellulose and sodium carboxymethyl hydroxyethyl
cellulose. Natural gums such as karaya, gum arabic, and gum
tragacanth can also be incorporated. Colloidal magnesium aluminum
silicate or finely divided silica can be used as component of the
thickening composition to further improve the composition's
texture. In certain embodiments, thickening agents in an amount of
about 0.5% to about 5.0% by weight of the total composition are
used.
Abrasives
[0118] Natural calcium carbonate is found in rocks such as chalk,
limestone, marble and travertine. It is also the principle
component of egg shells and the shells of mollusks. The natural
calcium carbonate abrasive of the invention is typically a finely
ground limestone which may optionally be refined or partially
refined to remove impurities. For use in the present invention, the
material has an average particle size of less than 10 microns,
e.g., 3-7 microns, e.g. about 5.5 microns. For example a small
particle silica may have an average particle size (D50) of 2.5-4.5
microns. Because natural calcium carbonate may contain a high
proportion of relatively large particles of not carefully
controlled, which may unacceptably increase the abrasivity,
preferably no more than 0.01%, preferably no more than 0.004% by
weight of particles would not pass through a 325 mesh. The material
has strong crystal structure, and is thus much harder and more
abrasive than precipitated calcium carbonate. The tap density for
the natural calcium carbonate is for example between 1 and 1.5
g/cc, e.g., about 1.2 for example about 1.19 g/cc. There are
different polymorphs of natural calcium carbonate, e.g., calcite,
aragonite and vaterite, calcite being preferred for purposes of
this invention. An example of a commercially available product
suitable for use in the present invention includes Vicron.RTM.
25-11 FG from GMZ.
[0119] Precipitated calcium carbonate is generally made by
calcining limestone, to make calcium oxide (lime), which can then
be converted back to calcium carbonate by reaction with carbon
dioxide in water. Precipitated calcium carbonate has a different
crystal structure from natural calcium carbonate. It is generally
more friable and more porous, thus having lower abrasivity and
higher water absorption. For use in the present invention, the
particles are small, e.g., having an average particle size of 1-5
microns, and e.g., no more than 0.1%, preferably no more than 0.05%
by weight of particles which would not pass through a 325 mesh. The
particles may for example have a D50 of 3-6 microns, for example
3.8=4.9, e.g., about 4.3; a D50 of 1-4 microns, e.g. 2.2-2.6
microns, e.g., about 2.4 microns, and a D10 of 1-2 microns, e.g.,
1.2-1.4, e.g. about 1.3 microns. The particles have relatively high
water absorption, e.g., at least 25 g/100 g, e.g. 30-70 g/100 g.
Examples of commercially available products suitable for use in the
present invention include, for example, Carbolag.RTM. 15 Plus from
Lagos Industria Quimica.
[0120] In certain embodiments the invention may comprise additional
calcium-containing abrasives, for example calcium phosphate
abrasive, e.g., tricalcium phosphate (Ca.sub.3(P0.sub.4).sub.2),
hydroxyapatite (Ca.sub.10(P0.sub.4).sub.6(OH).sub.2), or dicalcium
phosphate dihydrate (CaHP0.sub.4.2H.sub.2O, also sometimes referred
to herein as DiCal) or calcium pyrophosphate, and/or silica
abrasives, sodium metaphosphate, potassium metaphosphate, aluminum
silicate, calcined alumina, bentonite or other siliceous materials,
or combinations thereof. Any silica suitable for oral care
compositions may be used, such as precipitated silicas or silica
gels. For example synthetic amorphous silica. Silica may also be
available as a thickening agent, e.g., particle silica. For
example, the silica can also be small particle silica (e.g.,
Sorbosil AC43 from PQ Corporation, Warrington, United Kingdom).
However the additional abrasives are preferably not present in a
type or amount so as to increase the RDA of the dentifrice to
levels which could damage sensitive teeth, e.g., greater than
130.
Water
[0121] Water is present in the oral compositions of the invention
(e.g., Composition 1.0 et seq). Water, employed in the preparation
of commercial oral compositions should be deionized and free of
organic impurities. Water commonly makes up the balance of the
compositions and includes 5% to 45%, e.g., 10% to 20%, e.g.,
25-35%, by weight of the oral compositions. This amount of water
includes the free water which is added plus that amount which is
introduced with other materials such as with sorbitol or silica or
any components of the invention. The Karl Fischer method is a one
measure of calculating free water.
Humectants
[0122] Within certain embodiments of the oral compositions (e.g.
Composition 1.0 et seq), it is also desirable to incorporate a
humectant to reduce evaporation and also contribute towards
preservation by lowering water activity. Certain humectants can
also impart desirable sweetness or flavor to the compositions. The
humectant, on a pure humectant basis, generally includes 15% to 70%
in one embodiment or 30% to 65% in another embodiment by weight of
the composition.
[0123] Suitable humectants include edible polyhydric alcohols such
as glycerine, sorbitol, xylitol, propylene glycol as well as other
polyols and mixtures of these humectants. Mixtures of glycerine and
sorbitol may be used in certain embodiments as the humectant
component of the compositions herein.
[0124] The present invention in its method aspect involves applying
to the oral cavity a safe and effective amount of the compositions
described herein.
[0125] The compositions and methods according to the invention
(e.g., Composition 1.0 et seq) can be incorporated into oral
compositions for the care of the mouth and teeth such as
toothpastes, transparent pastes, gels, mouth rinses, sprays and
chewing gum.
[0126] As used throughout, ranges are used as shorthand for
describing each and every value that is within the range. Any value
within the range can be selected as the terminus of the range. In
addition, all references cited herein are hereby incorporated by
reference in their entireties. In the event of a conflict in a
definition in the present disclosure and that of a cited reference,
the present disclosure controls. It is understood that when
formulations are described, they may be described in terms of their
ingredients, as is common in the art, notwithstanding that these
ingredients may react with one another in the actual formulation as
it is made, stored and used, and such products are intended to be
covered by the formulations described.
[0127] The following examples further describe and demonstrate
illustrative embodiments within the scope of the present invention.
The examples are given solely for illustration and are not to be
construed as limitations of this invention as many variations are
possible without departing from the spirit and scope thereof.
Various modifications of the invention in addition to those shown
and described herein should be apparent to those skilled in the art
and are intended to fall within the appended claims.
Example 1
TABLE-US-00001 [0128] TABLE 1 Dentifrice Formulation A Ingredient
Weight % DEMINERALIZED WATER Q.S. (e.g., 15-35%) CITRIC ACID - 0.20
ANHYDROUS USP, EP TRISODIUM CITRATE 1.0 DIHYDRATE - USP STANNOUS
FLUORIDE, USP 0.454 Zinc Phosphate, hydrate 0.5-2.0% SORBITOL -
38.0-43.0% NON-CRYSTAL - 70% SOLN USP, EP POLYETHYLENE GLYCOL 2.0
600 Thickeners 1.5-2.0% STANNOUS 0.2-1.5% PYROPHOSPHATE Abrasives
20.0 TETRASODIUM 2.0 PYROPHOSPHATE - FINE FCC Anionic Surfactant
1.5 Amphoteric Surfactant 1.25 Flavors, Colors and Sweeteners
1.0-2.0 99%-101% Glycerin 4.0 Total Components 100.0
Example 2
TABLE-US-00002 [0129] TABLE 2 Stannous Stability Initial Aged
Initial Aged Aged Aging Time % Sol. % Sol. % Sol. % Sol. Initial %
Sol. Description pt Tin Tin Zn Zinc % F F SnF + 1% Initial 25 C.
0.37 0.48 1117 ZnP, 0.2% 4 wks(40 C.) 0.26 0.25 1030 SnPyro, 1.2% 8
wks(40 C.) 0.29 0.24 1042 Buffer 13 wks(40 C.) 0.27 0.28 981
(Composition A) SnF + 1% Initial 25 C. 0.4 0.24 1116 ZnP, 0.3% 4
wks(40 C.) 0.3 0.25 1047 SnPyro, 1.2% 8 wks 0.31 0.25 1026 Buffer
13 wks 0.3 0.25 956 (Composition B) SnF + 1% Initial 25 C. 0.51
0.27 1105 ZnP, 0.5% 4 wks(40 C.) 0.47 0.31 985 SnPyro, 1.2% 8 wks
(40 C.) 0.49 0.3 899 Buffer 13 wks 0.50/0.45 0.35/0.32 1010/799
(Composition (25 C./40 C.) C) SnF + 1% 0.65 0.25 ZnP, 0.75% 4 wks
0.44/0.40 0.26/0.20 1052/981 SnPyro, 1.2% (25 C./40 C.) Buffer 8
wks (Composition 13 wks D) SnF + 1% 0.59 0.23 1112 ZnP, 1% 4 wks
0.56/0.53 0.26/0.29 1042/981 SnPyro, 1.2% (25 C./40 C.) Buffer 8
wks 0.58/0.55 0.25/0.27 1024/909 (Composition 13 wks 0.58/0.54
0.29/0.28 979/874 E)
Example 3
[0130] Table 3 demonstrates the buffer composition used in above
Examples 1-3.
TABLE-US-00003 TABLE 3 Buffer System (wt %) Test Comp. Sodium
Citrate* Citric Acid Test Compositions w/o 0.00 0.00 Buffer
Compositions with 1.2% 1.0 0.2 Buffer
The water concentration of the above formulations is between 17.0%
to 21.0% by wt. These are considered "high water" formulations.
Therefore, the Applicants have addressed the instability of
stannous ions without having to resort to either a) low water
formulations; or b) dual phase compositions.
Example 4
TABLE-US-00004 [0131] TABLE 4 Stannous Uptake in Aerobic Biofilm
(units in (ppm)) 1.sup.st 2.sup.nd 3.sup.rd 4.sup.th 5.sup.th
6.sup.th Trt. Trt. Trt. Trt Trt Trt SnF + 1% ZnP, 3.19 8.71 11.6
0.2% SnPyro, 1.2% Buffer (Comp. 1) SnF + 1% ZnP, 3.69 5.27 7.98 1.2
10.59 12.52 0.3% SnPyro, (3.88) (10.44) (12.91) 1.2% Buffer (Comp.
2) SnF + 1% ZnP, 6.21 13.69 16.82 0.5% SnPyro, 1.2% Buffer (Comp.
3) SnF + 1% ZnP, 6.18 8.91 14.98 21.74 17.31 20.98 0.75% SnPyro,
1.2% Buffer (Comp. 4) SnF + 1% ZnP, 7.27 10.84 13.87 17.71 23.58
23.07 1.0% SnPyro, (6.81) (15.59) (25.99) 1.2% Buffer, (Comp. 5)
SnF + 1% ZnP, 6.9 9.92 16.48 18.02 18.91 20.98 1.0% SnPyro, 1.2%
Buffer, 12.3% Water (Comp. 6) 0.454% 1.61 2.17 3.41 3.42 6.34 4.56
SnF, Zn (1.11) (2.69) (7.05) Lactate (Positive Control) * Numbers
included in parenthesis indicate a second experimental run was
conducted. ** The designation "Trt" is understood to refer to
"Treatment". *** "Buffer" refers to an 1.2% by wt. organic acid
buffer comprising 1.0% by wt Sodium Citrate, and 0.2% by wt. Citric
Acid. The % wt. of the Sodium Citrate and Citric Acid refers to
their amounts relative to entire composition.
[0132] The aerobic biofilm model quantifies the ability of the
compound to prevent maturation of biofilm consisting of salivary
inoculum on an artificial tooth surface (or hydroxyapatite (HAP)),
through repeat treatment during a 5-day period. On Day 1,
Hydroxyapatite discs on an Active Attachment Lid are incubated in
clarified, sterilize-filtered saliva to form pellicle, treated,
inoculated in whole human saliva suspended in media, and incubated
before repeating treatment at end of day. The treatments are
repeated every morning on Day 2-5.
[0133] After each treatment, each HAP discs containing biofilm are
transferred to tubes containing 1 ml Aqua regia which is a mixture
of nitric acid and hydrochloric acid used to dissolve metals or
acid digest. The tubes are kept under a fume hood overnight to
ensure full acid digestion. The samples are centrifuged to pellet
the debris. The acid supernatant (aqueous portion) is transferred
into another clean tube and brought up to volume to make a 10% acid
solution using sterile water (1 ml supernatant: 9 ml water). This
sample is sent to analytical for metal detection. The data is
represented as parts per million (ppm) and as well as metal uptake
over 6 treatments.
[0134] As can be seen in Table 4, compositions with SnF, zinc
phosphate, demonstrate much increased stannous uptake in the
aerobic biofilm assay as compared to market backbone formulations
containing Zinc Lactate as the zinc source, and Stannous Fluoride
as the source for stannous.
* * * * *